The PORTRAIT Study

NCT04222452 | Unknown

• 1 other identifier: STH20707
• Study Type: observational
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

Clinical Consequences of Adults Presenting with Hypophosphatasia with Special Focus on Gait, Bone Microstructure and Cognition: The PORTRAIT study Hypophosphatasia (HPP) is an inherited condition that leads to weak bones. Early childhood forms are severe and easily recognized. Adult forms can vary in severity. HPP is often missed by doctors or confused with osteoporosis. This is important because the usual osteoporosis treatments may be harmful to patients with HPP and increase the risk of broken bones. One of the reasons it is missed is a lack of research describing the typical features of HPP, so doctors don't recognize the signs, and don't know when or how to test for it. The PORTRAIT Study will help increase understanding of the burden of disease of HPP on patients. The aim is to examine the effects of HPP on bone structure and strength, physical functioning, cognition, and quality of life. Researchers will study adults with HPP and healthy age- and gender-matched individuals. Blood samples will be collected after an overnight fast. Researchers will use these samples to measure markers of HPP and bone health. Medical history and lifestyle, quality of life and cognitive function will be assessed using questionnaires. Bone mineral density, body composition and bone structure and strength will be measured using dual energy x-ray absorptiometry and high resolution peripheral quantitative computed tomography. Physical functioning will be assessed as participants perform a series of physical performance and gait tests. Magnetic resonance images of the lower limbs will be matched-up with the physical functioning data to create patient-specific musculoskeletal models. Cognitive function tests will be performed to assess cognition and mental health. To reveal the burden of disease of HPP, the data collected from patients with HPP will be compared to that collected from healthy controls.

Conditions

Hypophosphatasia

Keywords

Burden of disease; Bone microstructure; Cognition; Physical functioning

Outcome Measures

Primary Outcomes (1)

• Clinical consequences and disease burden of HPP on the total score (balance + Gait) achieved during the Tinetti Performance Oriented Mobility Assessment (POMA)

  Differences in gait: HPP patients versus healthy controls

  Through study completion, average 18 months

Secondary Outcomes (2)

• Clinical consequences and disease burden of HPP on volumetric Bone Mineral Density (vBMD, in g/cm3)

  Through study completion, average 18 months

• Clinical consequences and disease burden of HPP on the total score achieved during the Montreal Cognitive Assessment (MoCA) Test

  Through study completion, average 18 months

Study Arms (2)

Hypophosphatasia patients (HPP)

Patients with known hypophosphatasia (HPP) as diagnosed using genetic testing.

Controls

Healthy individuals (controls) matched to the cases by gender and age.

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with HPP (cases) and healthy individuals (controls)

You may qualify if:

• HPP PATIENTS (CASES)
• Clinical diagnosis of HPP (with or without previous genetic test confirmation)
• Evidence of burden of disease (HPP) including abnormal gait, muscle weakness, pain, recurring fractures, slow healing fractures and/or bone deformities
• Age ≥ 18 years
• Able and willing to participate in the study
• Able to give written informed consent
• HEALTHY INDIVIDUALS (CONTROLS)
• Healthy men and women with normal bone mineral density (defined as a DXA bone mineral density T- score at the lumbar spine or total hip greater than -1).
• Age ≥ 18 years
• Able and willing to participate in the study
• Able to give written informed consent

You may not qualify if:

• HPP PATIENTS (CASES)
• Individuals with BMI\<18, or BMI\>30 kg/m2
• Other conditions known to affect serum ALP and PLP
• Coeliac disease, B12 deficiency, untreated hypothyroidism, Wilson's disease
• Taking nutritional supplements containing vitamin B6 within past two weeks
• History of, or current:
• Severe ischaemic heart disease, rheumatoid arthritis, ankylosing spondylitis, cancer (concurrent)
• History of, or current neurological diseases affecting the neuromuscular system including Parkinson's disease, CVA, muscular dystrophy, myasthenia, cerebral trauma, peripheral neuropathy
• Treatment for more than 3 months in a year or under treatment with oral corticosteroids
• History of any long term immobilization (duration greater than three months)
• Conditions or surgery which prevent the acquisition or analysis of musculoskeletal images
• Use of medications or treatment known to affect bone metabolism other than calcium/vitamin D supplementation.
• Alcohol intake greater than 21 units per week
• Pregnant or breast feeding
• HEALTHY INDIVIDUALS (CONTROLS)

Sponsors & Collaborators

• Sheffield Teaching Hospitals NHS Foundation Trust: lead
• University of Sheffield: collaborator

Study Sites (1)

The University of Sheffield

Sheffield, South Yorkshire, S5 7AU, United Kingdom

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood samples (full blood and serum)

MeSH Terms

Conditions

Hypophosphatasia

Condition Hierarchy (Ancestors)

Metal Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Richard Eastell, MD

  University of Sheffield

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 23, 2019
• First Posted: January 10, 2020
• Study Start: July 12, 2021
• Primary Completion: February 28, 2023
• Study Completion: February 28, 2023
• Last Updated: November 2, 2022

Record last verified: 2022-08

Locations

GB (1)